TXNRD2
Chr 22ARthioredoxin reductase 2
Also known as: GCCD5, SELZ, TR, TR-BETA, TR3, TRXR2, TXNR2
The protein encoded by TXNRD2 is a mitochondrial selenoenzyme that reduces thioredoxin and maintains mitochondrial redox homeostasis by scavenging reactive oxygen species. Mutations cause glucocorticoid deficiency 5, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants (pLI near 0), which is consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
1093 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 211 | 0 | 211 |
Likely Pathogenic | 0 | 0 | 8 | 0 | 8 |
VUS | 45 | 346 | 61 | 4 | 456 |
Likely Benign | 0 | 9 | 145 | 178 | 332 |
Benign | 0 | 1 | 53 | 1 | 55 |
Conflicting | — | 24 | |||
| Total | 45 | 356 | 478 | 183 | 1,086 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TXNRD2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools